Trimethoprim stimulates T-cells through metabolism-dependent and -independent pathways

Sabah El-Ghaiesh; Joseph P. Sanderson; John Farrell; Sidonie N. Lavergne; Wing Kin Syn; Munir Pirmohamed; B. Kevin Park; Dean J. Naisbitt

doi:10.1021/tx2001256

Trimethoprim stimulates T-cells through metabolism-dependent and -independent pathways

Sabah El-Ghaiesh, Joseph P. Sanderson, John Farrell, Sidonie N. Lavergne, Wing Kin Syn, Munir Pirmohamed, B. Kevin Park, Dean J. Naisbitt

Research output: Contribution to journal › Article › peer-review

Abstract

Pathways of drug-specific T-cell stimulation have not been fully defined. The aim of this study was to use T-cell clones from a patient hypersensitive to the drug trimethoprim to characterize the involvement of drug metabolism and processing in antigen presentation and cross-reactivity patterns. The MHC-restricted CD4+ and CD8+ T-cell response was dependent on the presence of antigen-presenting cells, and both processing-dependent and -independent pathways of antigen presentation were detected. Stimulation of certain clones was blocked through inhibition of drug-metabolizing enzyme activity. Trimethoprim clones were additionally stimulated with diaveridine and pyrimethamine but not other closely related structures.

Original language	English (US)
Pages (from-to)	791-793
Number of pages	3
Journal	Chemical Research in Toxicology
Volume	24
Issue number	6
DOIs	https://doi.org/10.1021/tx2001256
State	Published - Jun 20 2011
Externally published	Yes

ASJC Scopus subject areas

Toxicology

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10.1021/tx2001256

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abstract = "Pathways of drug-specific T-cell stimulation have not been fully defined. The aim of this study was to use T-cell clones from a patient hypersensitive to the drug trimethoprim to characterize the involvement of drug metabolism and processing in antigen presentation and cross-reactivity patterns. The MHC-restricted CD4+ and CD8+ T-cell response was dependent on the presence of antigen-presenting cells, and both processing-dependent and -independent pathways of antigen presentation were detected. Stimulation of certain clones was blocked through inhibition of drug-metabolizing enzyme activity. Trimethoprim clones were additionally stimulated with diaveridine and pyrimethamine but not other closely related structures.",

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AU - El-Ghaiesh, Sabah

AU - Sanderson, Joseph P.

AU - Farrell, John

AU - Lavergne, Sidonie N.

AU - Syn, Wing Kin

AU - Pirmohamed, Munir

AU - Park, B. Kevin

AU - Naisbitt, Dean J.

PY - 2011/6/20

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N2 - Pathways of drug-specific T-cell stimulation have not been fully defined. The aim of this study was to use T-cell clones from a patient hypersensitive to the drug trimethoprim to characterize the involvement of drug metabolism and processing in antigen presentation and cross-reactivity patterns. The MHC-restricted CD4+ and CD8+ T-cell response was dependent on the presence of antigen-presenting cells, and both processing-dependent and -independent pathways of antigen presentation were detected. Stimulation of certain clones was blocked through inhibition of drug-metabolizing enzyme activity. Trimethoprim clones were additionally stimulated with diaveridine and pyrimethamine but not other closely related structures.

AB - Pathways of drug-specific T-cell stimulation have not been fully defined. The aim of this study was to use T-cell clones from a patient hypersensitive to the drug trimethoprim to characterize the involvement of drug metabolism and processing in antigen presentation and cross-reactivity patterns. The MHC-restricted CD4+ and CD8+ T-cell response was dependent on the presence of antigen-presenting cells, and both processing-dependent and -independent pathways of antigen presentation were detected. Stimulation of certain clones was blocked through inhibition of drug-metabolizing enzyme activity. Trimethoprim clones were additionally stimulated with diaveridine and pyrimethamine but not other closely related structures.

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Trimethoprim stimulates T-cells through metabolism-dependent and -independent pathways

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